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There are a few things that make a great spouse or friend. One of those things is not twerking like Miley Cyrus at the VMA's. The other in my opinion is lifting you up when you’re down but also keeping you grounded when you get a bit too annoying confident. Amanda unknowingly is an expert at the latter (yes, you’re also good at encouraging me as well). Over the past year she has asked me many basic medical questions, typically at the dinner table, all of which I seemingly can never answer appropriately. Thus, was the inception of this series – “So My Wife Asked Me…”. These particular blogs will be a bit more basic in nature but hopefully informative nonetheless. Because let’s face it, one of the worst feelings as a doctor is being unable to answer a simple question. So Amanda’s question was…

“Where do Hiccups come from and what should I do to stop them?”

I retort back with “good question” aka my 2-second time
filler when I don’t have a satisfactory answer.
My typical answer to this question is that it’s diaphragmatic
irritation/spasm, most commonly idiopathic. The most common known etiologies being central nervous
system processes like CVAs. Finally, what to do about them? I got nothing for
ya because really everyone has their own superstitious way about eliminating
hiccups but they are all too zany to make actual sense. Chronic, pathological hiccups are another
story with many people suggesting
chlorpromazine but the only medication I’ve actually used was Baclofen for a
patient with a posterior CVA.

Let’s start with where they come from. The mechanism of the
actual hiccup on a macro level is easier to explain than the mechanism on the
micro level. Most sources agree that the hiccup is indeed sudden contraction of
the diaphragm in conjunction with the closure of the glottis. It’s also proposed
that there is a reflex arc involved with the afferent portion being the vagus
and phrenic nerves along with the sympathetic chain. The efferent pathway is
thought to be the recurrent laryngeal nerve that induces the glottis closure.
That is pretty much the general consensus because those are the nerves that
innervate those specific structures.

Regarding the etiology? Well the list of potential causes is
literally over 100 items long, at least according to Dynamed as well as
looking at other sources. You know what that means? Your grandma, your dumb
friend who insists he/she is always right, and the guy making awkward
conversation with you on the bus are probably all correct. Everything has potentially
been linked to hiccups. The few epidemiologic studies there are about hiccups
are pretty laughable and only look at intractable (> 48 hr) hiccups. There’s
one from 1968 that looked at 220 cases [1]
and there’s one that looked at 20 cases of chronic hiccups in 1992. [2]
The ancient 1968 study (per UpToDate since I can’t access the article) found
the majority of patients wereolder males (~80%), many of which had vascular (20%)
and CNS comorbidities (17%). The newer study from 1992 found reflux esophagitis
to be the most frequent cause of intractable hiccups (10 of the 20 cases).

So now we know anything is possible when it comes to hiccups etiologies. But how do we treat this scourge? I like to break the
treatment down into 3 categories 1) Things you hear second hand that people
insist work but inevitably fail 2) Interventions I might give consideration 3) Hail
Mary Group - interventions that I’d only consider in the most refractory of
cases.

Starting with the non-pharmacologic, less plausible
interventions, I found there are exactly 0 studies regarding the use of these
in acute hiccups. There really is no evidence so I’ll go ahead and list these
on order of least ridiculous to most ridiculous.

Holding breath

Breathing into a paper bag

Causing fright

Biting a freaking lemon

Inducing sneezing with black pepper

Applying pressure to the bridge of nose, upper
lip, or eyebrow area (a friend’s favorite)

Swallowing difficult to swallow items such as
granulated sugar, peanut butter, or molasses

Drinking water from the opposite side of the cup

Lifting the uvula with a spoon…

Finally, sexual intercourse! – Was actually
found to stop intractable hiccups in a single case report [3]

Then there are a few they recommend that clinicians can try
such as:

Induction of vomiting with emetic

Breathing 5% carbon dioxide

Stimulating vagus nerve by supraorbital pressure

Those all sound equally if not more ridiculous. I can’t help
but think of someone gouging a person’s eyes when it comes to supraorbital
pressure. I was considering posting a picture for humor’s sake but found all
the google images to be very disturbing. So I didn't. You're welcome.

Moving to things I’d actually consider treating a patient
with or doing myself. In this category I’d either want a physical maneuver that
was somewhat plausible for stopping the reflex arc or medication with a proven
track record but also without a heavy-duty side effect profile. Here were my
choices for this:

The first four I
chose to add to my repertoire because they are more known to cause a vagal
response. It’s more plausible to see these overriding the reflex arc than let’s
say… biting a lemon. The last four have decent evidence to moderate evidence
but without too harsh of a side effect profile. Acupuncture and Baclofen
actually have the best evidence. There have actually have been a number of
randomized trials showing acupuncture to be superior to Reglan and placebo. An
analysis of 3 randomized trials of 162 patients found a risk ratio of 1.87 (95%
CI 1.26-2.78) [5]. However, a Cochrane review found that the type of acupuncture was significant as 4 needle and 1 hour
acupuncture duration was superior (p < 0.05) to 3 needle and 30 minute
acupuncture. [6]

Out of all the
prescription medications, Baclofen has the best evidence, especially for
decreasing severity of hiccups. This is mainly based on a case series of 37
patient with intractable hiccups which found Baclofen 5mg TID (titrated up to
75 mg/day) completely resolved 53% and considerably improved another 29% of
patients seen in follow up. [7] There
was also a tiny (n=4?!) randomized trial that somehow found significant
improvement in severity but no frequency of hiccups. [8]
Reglan and Gabapentin have also had individual case series show complete
resolution in 100% (and within 30 minutes to boot) and 81% of patients. The
Reglan option is particularly appealing since it’s a commonly used medication
and apparently has had shown good effect in the past.

Last but not least, the Hail Mary group. Basically the only
candidate in this group is Chlorpromazine (Thorazine) which is actually the
only FDA approved drug for intractable hiccups. It has decent evidence showing
complete resolution of intractable hiccups in 41 of 50 patients in a case
series while reducing symptoms in another five. [9] But
really, EPS symptoms scare me. And although Chlorpromazine is much less likely
to cause EPS symptoms than other traditional antipsychotics like Haldol, I’m sure
patients would like to ideally control their own bodily movements.

There are other less savory interventions like phrenic nerve
blocks, Haldol, and various surgeries and procedures that you could also try if
you want to scrape the bottom of the barrel. But if you passed the gauntlet and
are still refractory at this point you are probably pretty ill (Chemotherapy,
CVA) and might be willing to try these interventions.

Wrapping up, I learned that it is indeed OK to say “we don’t know” when it comes to hiccups and that your annoying friend/family member is probably correct when they think global warming, signals from the TV, or Miley Cyrus' twerking can cause hiccups. I was also able to refine my algorithm a bit for hiccups (Maneuvers > likely Reglan > Baclofen > Gabapentin >> Thorazine). So here’s to another question of Amanda’s I can now confidently answer. At least until next time she ruins my self-esteem keeps me grounded.